van den Wijngaard, Pascalle Aniek (2023) The association of 11β-HSD1 with graft failure in kidney transplant recipients. thesis, Medicine.
Full text available on request.Abstract
Background. Kidney transplantation is the best treatment for end-stage kidney disease, this treatment often includes treatment with prednisolone. Consequently, this results in hypothalamic-pituitary-adrenal-axis suppression and increased activity of the enzyme involved in cortisol and prednisolone regeneration: 11-β hydroxysteroid dehydrogenase type 1 (11ß- HSD1). We investigated the 11ß-HSD1 enzyme activity in prednisolone treated kidney transplant recipients (KTR) compared to healthy controls and its association with graft failure in KTR. Methods. In a prospective cohort study of 672 KTR and 103 healthy donors, 24-hour urinary excretion of glucocorticoid metabolites were measured using validated gas chromatography tandem mass spectrometry. The 24-hour urinary excretion of these metabolites were used as measures of endogenous glucocorticoid production. The (THF + allo-THF)/THE was used as measure for 11ß-HSD1 activity. Results. The excretion of all the metabolites of cortisol and the total glucocorticoid metabolite excretion were significantly lower in KTR compared with healthy controls (P < .001). Activity of the 11ß-HSD1 enzyme was higher in KTR (1.6 [1.2-2.2]) compared to controls (0.95 [0.76-1.14], P <.001). In addition, increased 11ß-HSD1 activity in KTR was associated with increased risk of graft failure independent of sex, HDL cholesterol, receiving a living donor kidney and use of calcineurin inhibitors. (HR 9.7 95%CI [3.8-25.1], P< .001). Conclusion. In prednisolone treated KTR endogenous glucocorticoid production is decreased, while 11ß-HSD1 activity is increased. Increased 11ß- HSD1 activity is highly associated with increased risk of graft failure in KTR. These results warrant further research into the role of 11ß-HSD1 activity on the risk of renal transplant failure and more specifically into the role of specific enzyme inhibition.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | van Beek, Dr. A.P. |
| Faculty: | Medical Sciences |
| Date Deposited: | 05 May 2023 13:31 |
| Last Modified: | 05 May 2023 13:31 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3511 |
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